Dihydrotanshinone I inhibits aortic valve interstitial cell calcification via the SMAD1/5/8/NF-KB/ERK pathway

作者全名："Wang, Yue; Weng, Yaguang; Li, Xian; Huang, Qin; Xiang, Yi; Li, Xiaorong; Shi, Qiong"

作者地址："[Wang, Yue; Weng, Yaguang; Huang, Qin; Xiang, Yi; Li, Xiaorong; Shi, Qiong] Chongqing Med Univ, Sch Lab Med, Minist Educ, Key Lab Diagnost Med, 1 Med Sch Rd, Chongqing 400016, Peoples R China; [Li, Xian] Chongqing Med Univ, Dept Pathol, Chongqing, Peoples R China"

通信作者："Shi, Q (corresponding author), Chongqing Med Univ, Sch Lab Med, Minist Educ, Key Lab Diagnost Med, 1 Med Sch Rd, Chongqing 400016, Peoples R China."

来源：BIOMEDICINE & PHARMACOTHERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000663686900009

JCR分区：Q1

影响因子：7.5

年份：2021

卷号：139

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Calcific aortic valve disease; Porcine aortic valve interstitial cells; DHI; Osteogenic differentiation

摘要："Objectives: In calcific aortic valve disease (CAVD), the valve interstitial cells (VIC) osteogenic phenotype changes can lead to thickening and calcification of the valve leaflets,eventually lead to restricted valve movement and life-threatening. This study aims to investigate the effect and mechanism of dihydrotanshinone I (DHI) on osteogenic medium (OM) induced osteogenic phenotypic transition of porcine valve interstitial cells (PVICs), which can provide theoretical and scientific basis for clinical intervention in CAVD. Methods and results: Immunohistochemical methods were used to detect the expression of osteogenic indicators Runx2, OPN and inflammation indicators IL-1 beta and p-NF-KB in valve specimens of CAVD patients(N = 3) and normal controls(N = 1). PVICs stimulated by osteoblastic medium (OM) were treated with or without DHI. CCK8, ALP and Alizarin Red S staining were used to detect cell growth and calcification, respectively. The results showed that under the treated with DHI, compared with OM, the formation of calcium nodules was reduced, and the expression of calcification-related markers Runx2 and OPN were down-regulated, which quantified by qRTPCR and western blot. In addition, on the basis of OM induction, DHI also inhibited the phosphorylation of the NF-KB/ERK1/2 and SMAD1/5/8 signaling pathway. Conclusion: DHI (10 & micro;M) treatment can reverse the osteogenic phenotypic transition of PVICs induced by osteogenic medium, and the mechanism may be related to NF-KB?ERK 1/2 and Smad1/5/8 pathways."

基金机构：Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [NSFC 81672103]

基金资助正文："The trial was supported by the Natural Science Foundation of China (NSFC 81672103 to QS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."